Correlated evolution of synonymous and nonsynonymous sites in Drosophila.

Recent work has shown that Drosophila melanogaster genes with fast-evolving nonsynonymous sites have lower codon usage bias. This pattern has been attributed to interference between positive selection at nonsynonymous sites and weak selection on codon usage. Here we have looked for this correlation in a much larger and less biased dataset, comprising 630 gene pairs from D. melanogaster and D. yakuba. We confirmed that there is a negative correlation between the rate of nonsynonymous substitutions (d(N)) and codon bias in D. melanogaster. We then tested the interference hypothesis and other alternative explanations, including one involving gene expression. We found that d(N) indeed correlates with the level of gene expression. Given that gene expression is a strong determinant of codon bias, the relationship between d(N) and codon bias might be a by-product of gene expression. However, our tests show that none of the hypotheses we consider seem to explain the data fully.